Sunday, July 31, 2011

Everyone loves reading about the Siberian fox experiment because domesticated silver foxes are so damn cute. There’s something deeply appealing about the idea of a cuddly fox. And the experiment raised some interesting questions about domestication. Could domestication really happen in just eight generations? (Apparently.) Domestication must just affect the brain and not the rest of the body, right? (Apparently not – domesticated foxes can have characteristic coat color changes, floppy ears, and curly tails, similar to morphologic differences between dogs and wolves.) But a research population of domesticated foxes hasn’t been maintained since the sixties just because they are cute. We’re still learning things from them. Like what? Get ready for some well-aged papers; a lot of this work was done back in the eighties.

Hormone and neurotransmitter soup

We use the hormone cortisol as a marker of stress: if you have more cortisol in your blood, you’re probably more stressed. It turns out, perhaps not surprisingly, that domesticated foxes have lower basal levels of cortisol than their unselected counterparts (Oskina, 1992). Their cortisol levels also don’t go up as high during a stressful experience as do the cortisol levels of unselected foxes (Harri, 2003). Personally, I think cortisol is going to play a key role in the mechanism of why domesticated animals are less flighty than wild ones. Cortisol levels influence the production of adrenaline: if you have more cortisol in your system, you are liable to make more adrenaline (Kvetnansky, 2009). If you have more adrenaline in your system, you are going to react more strongly to scary stimuli – in other words, your flight distance is going to increase. (Quick review – domesticated foxes were bred by selection for decreased flight distance from humans.) My friends and I noticed during our highly stressful first year of veterinary school, when our cortisol levels were certainly high, that were were inexplicably jumpy. One friend reported that she was so startled by the noise of a dropped glass that she actually screamed.

As for the ever-popular serotonin, the “happy hormone,” domesticated foxes have more of it in their midbrains and hypothalamuses (Popova, 1991). Yes, the same hypothalamus that is the beginning of the hypothalamic-pituitary-adrenal axis, which ends in the release of cortisol. Oh, and which is inhibited by having more cortisol already in the system, in a negative feedback loop.

There is nothing cuter than a baby domesticated fox

Wolf cubs have a much shorter socialization window than dog puppies, and this might be part of why it is so difficult to socialize a wolf cub to humans. It turns out that unselected fox kits have a shorter socialization window than domesticated fox kits, too. Prime socialization time in both lines seems to start around 30-35 days, when the kits can see and hear and are mobile enough to explore their surroundings. Like most very young animals, fox kits of this age aren’t as fearful as their adult counterparts; they have a chance to learn what is dangerous and what is not in their particular environment. A longer socialization window gives you more chances to learn that a variety of beings are not dangerous to you, but in the wild it also gives you a greater chance of getting eaten by something that is dangerous to you when you wander up to say hello to it.

Domesticated fox kits start showing fear of new objects after age 60-65 days. Unselected kits, on the other hand, start fearing novel things at day 40-45 (Belyaev, 1985). We don’t know what exactly causes this difference in a preprogrammed socialization window, but it’s very helpful to have these populations as we look for the cause.

An even lower level of programming

In recent years, researchers have had new tools to use in exploring the mechanisms of domestication in foxes, especially since the canine genome was sequenced. Comparing gene expression in the wolf and the dog is problematic, because they necessarily live in such different environments. Comparing gene expression in two populations of foxes raised in identical conditions is potentially much more fruitful. This research is in the early days. But as we learn more about the canine genome I think we’ll start finding some really interesting differences between the lines of domesticated and unselected foxes. My personal belief is that we’ll find subtle differences – maybe, rather than differences in actual genes, we’ll see changes in promoter sequences, which cause significant genes to be up or down regulated.

We’ve learned a lot from the Russian domesticated foxes so far, but we have a long way yet to go. We still have no real idea exactly what is at the root of the difference between a domesticated and undomesticated animal. Does the change in development affect cortisol and serotonin levels, or vice versa? Does just a single genetic modification cause all the physiologic changes we see? Or are we looking for a set of modifications? Hopefully the new genomic tools we’re developing will allow us to get to the bottom of the mystery.

Saturday, July 23, 2011

It’s challenging to breed purebred dogs well. You have to balance appearance, health, and temperament, and of course by “health” I actually mean “2598237 different possible inherited diseases.” You breed or buy the best animal you can (no small task in itself), you compete with it to prove its ability and conformance to the breed standard, and then when it is an adult the time comes to breed it. Before you breed, you have to make sure the animal is physically healthy. You perform perhaps thousands of dollars worth of tests towards this goal. If your star fails any one of them, you should consider not breeding it, even if it is otherwise a great breeding prospect. If it fails a really important test — like the assessment of the likelihood of developing hip dysplasia in a breed that is notorious for its hip problems, like the golden retriever — then you really shouldn’t breed the animal.

Time was, dog breeders had big kennels, with dozens of dogs. If one of them turned out to have an inheritable health problem, it was fairly easy to just remove that animal from the breeding program. After all, if you have 50 dogs and can only breed 49 of them, what’s the big deal? These days, people have less land, and dog breeders tend to have smaller numbers of dogs. So what happens if you are the owner of a single, beloved pet and you really want to try to improve the breed by having a litter from this pet? You show, you compete, you have health tests, and the animal fails the test for healthy hips. Now it’s not just a question of not breeding a single animal. Instead, it’s a question of not being able to breed at all, unless you get another dog and start over. What if that one has a health problem too, and you really don’t want to have three dogs in your house?

It’s a tangled issue. Personally, I think dogs do better in homes than in kennels, generally speaking (although I recognize that there are some private kennels out there containing some very happy dogs). But I also think that if we are going to be selecting dogs for beauty, as we do with show dogs, we have a responsibility to not let health fall by the wayside. Making the breeding of healthy dogs easier is a good thing. It’s sad to think that the fact that more dogs are living inside as pets makes breeding responsibly more difficult.

Tuesday, July 19, 2011

It’s a long story, so stick with me. Let’s say you’re deeply involved in the dog world, and love a particular breed of dog. You breed to improve that breed. You have a young bitch that you are considering breeding. You start out by taking this bitch to dog shows, doing that circuit until the bitch has earned her championship after a number of wins at different shows. This shows that the bitch is conformationally excellent enough to be worth breeding. You may also work with the bitch in some other area, like competition obedience, tracking, or agility.

When the time comes to breed, there is more work to do. You have to make sure the bitch is genetically good material. You know what problems are common in the breed, so you test for those. There are some problems (like hip dysplasia) which are so common that breeders test for them in almost every breed; there are some that are more rare. Some tests are genetic tests done on DNA samples. Some are just the sorts of tests any vet might do to see if the levels of different chemicals in the blood are within normal ranges, or if they are suggestive of certain conditions. All these tests have to be done on both sire and dam.

Who’s the sire? You should pick out a sire that complements this bitch well. No animal is perfect. If the bitch’s biggest failing is her less than perfect hip conformation, then the sire should have really exceptional hip conformation, to balance that problem out. They should not be too closely related, either.

The right sire may live across the country or across the world from the bitch. If he’s far away, artificial insemination will be necessary (although some animals get transported quite a distance for sexual liaisons, and some bitches are artificially inseminated even though the dog is in the next room). When exactly should this occur? If the dog is prime breeding material, his semen will be very expensive, not to mention the fees for implanting it (more on that later). So you want to do it as few times as possible.

It’s also important to know as precisely as possible when the bitch ovulated, because this helps predict when she will give birth. So ovulation prediction is an important part of this process. It involves blood tests over multiple days, done by a veterinarian.

Once you know what the bitch’s three fertile days will be, how will you get the semen in? You can choose natural service (the old fashioned method), artificial insemination into the vagina, or intra-uterine insemination (surgical insemination directly into the uterus). This last approach is the most reliable, although of course it is also the most invasive and expensive.

If you don’t choose natural service, you may be getting either fresh semen (from the dog in the next room), fresh chilled and shipped overnight (from somewhere on your continent, collected the previous day), or frozen (from anywhere in the world, and possibly as venerable as twenty years old). Why would you artificially inseminate fresh semen, if the dog is right there? Some bitches can be cranky if they don’t approve of the dog on offer, and there can be violence. The owner of an expensive (or well loved!) stud dog might not wish to risk his injury.

Now it comes down to it. Many breeders will have spent thousands of dollars to get to this point. Some will have spent tens of thousands. They really, really want to have a successful impregnation. The fresher the semen, the more reliable it is. If the best possible sire is only providing frozen semen for whatever reason, the chances are significant that the bitch will not get knocked up. So what do you do?

On the bitch’s first fertile day, you use the frozen semen from the preferred sire. You hope that all her eggs get fertilized by this semen, but if some are left over, you call in the backup sire, someone local who can provide fresh semen. Hopefully any eggs that failed to get fertilized by the first sire will get handled by the second. You may well end up with puppies from each sire in the litter, but that’s fine; you can DNA test them to know who’s sired by whom. And that is how a puppy can have two daddies, or, at least, a litter can.

(Note: I skipped over the numerous ethical issues brought up in this story. For today, I just wanted to share with you some of the surprising tools available to dog breeders today.)

Monday, July 11, 2011

I just completed my two-week neurology rotation. You might think that, because I love dog brains, this would have been right up my alley. Actually, I love the parts of brains that help us learn, fear, trust, and love. Veterinary neurology, on the other hand, is a big game of Hunt the Lesion. A dog comes in uncoordinated and with a head tilt. Where in its brain, cranial nerves, or spinal cord is the problem?

A good neurologic exam can localize the problem to the cerebrum, the cerebellum, one or more of the cranial nerves, the spinal cord in front of the front legs, the spinal cord over the front legs, the spinal cord between the front and back legs, the spinal cord over the back legs, the spinal cord behind the back legs, or something more general (a diffuse muscle, nerve, or muscle/nerve junction problem). Once we had an idea where the problem was, we usually sent the animal in to the MRI scanner (a luxury at a large referral hospital; we received a lot of animals coming in just for the MRI, referred from places that don’t have them). This allowed us to see exactly where the lesion was, and to get some information about what kind of lesion it was (intervertebral disc extruded into the spinal canal? A stroke? Cancer?).

I did enjoy neurology, even though Hunt the Lesion isn’t my favorite game. There was a surprising amount of basic medicine to learn; I got a lot more comfortable with how to manage post-surgical animals (we did lots of vertebral surgeries), as well as how to approach a diagnosis (young animals are more likely to have congenital or infectious problems or to have eaten toxins; older animals are more at risk for stroke or cancer). Practicing basic medicine is always good! So it was an enjoyable rotation, but now I am really looking forward to my upcoming four whole weeks of elective time.

Sunday, July 3, 2011

When I was on my small animal medicine rotation a few months ago, I had a patient with bad kidney disease. This little dog was sixteen years old — about a hundred years in human terms — and very frail and thin. I got into the habit of calling her “Grandmother,” because she seemed so venerable. None of us had very high hopes for her long term recovery, not even her owner; we were just trying to give her a shot at a few more weeks of life by rehydrating her with IV fluids.

Two of the residents disagreed about our goals for this dog. One of them wanted to send her home as soon as possible, arguing that she didn’t have much time left and shouldn’t spend it in the hospital. The other argued that we should give the dog a few more days to wean her off of her IV fluids properly before sending her home, to give her the best chance. The second resident ended up handling the case, and the dog stayed in the hospital for those few extra days for some extra care before going home.

This week I encountered the same dog (and the same resident) in the hospital for a recheck. I hardly recognized the dog, and not just because I had never expected to see her again. She had put on weight and looked filled out and healthy. She was moving around the hospital under her own steam (when she was my patient, I had had to carry her outside to pee) with a happy trot. She was bright-eyed and curious. Her owner reported that she was even playing sometimes.

“Look,” the resident said, “sometimes we really can bring them back from the edge.”

At age sixteen, this dog doesn’t have much time left no matter how you look at it, but that doesn’t mean it was time to give up on her. The lesson had personal meaning for me. My fifteen year old cat, Kai, is currently battling kidney disease, heart disease, and stomach cancer (gastric lymphoma). Each of these diseases is serious; each has almost killed him at one point. Each time I have to decide whether to continue with him, I ask myself whether I am being silly, whether it is time to give up. The treatments are not invasive, but is there any point to them when I may just have weeks left with him? Then I look at how good his quality of life is (he steals food off my plate, sneaks outside when I am not looking and eats things he shouldn’t in my back yard, and uses foul language to tell the dogs what he thinks of them) and remember the lesson of the little sixteen year old dog. Sometimes, even when things look bleak, animals can make a remarkable recovery for a little while. If the treatments are not invasive and the animal is not in pain, it can be worth trying.

About the Dog Zombie

Jessica Perry Hekman, DVM, PhD is fascinated by dog brains. She is a postdoctoral associate at the Broad Institute of MIT and Harvard, where she studies the genetics of dog behavior. Her interests include the stress response in mammals, canine behavior, canine domestication, shelter medicine, animal welfare, and open access publishing. You may learn more about Jessica at www.dogzombie.com, or email her at jph at dogzombie dot com. All opinions expressed here are her own.

For the animal shall not be measured by man… They are not brethren, they are not underlings: they are other nations, caught with ourselves in the net of life and time, fellow prisoners of the splendor and travail of the earth. (Henry Beston)